Esophageal adenocarcinoma (EAC) is one of two major types of esophageal cancer, which causes 509,000 deaths worldwide annually. EAC diagnosis is made using the invasive, expensive, risky, and not universally accessible procedure, esophagogastroduodenoscopy (EGD). Thus, there is a pressing need for easier, safer, cheaper strategies for EAC diagnosis. Our novel strategy builds on exciting preliminary data in EAC patients involves a swallowable, retrievable sponge capsule device combined with a DNA methylation biomarker panel (JHU patent pending). Capsulomics, a new startup established specifically for this project, will commercialize this diagnostic assay, termed ?EsoSAVE,? for EAC detection. This Phase I STTR application contains three Specific Aims to implement this strategy. Aim 1 will optimize and validate the EsophaCap DNA extraction procedure. Aim 2 will generate a multi-parameter statistical model to further strengthen our promising methylation biomarkers. Aim 3 will validate the EsoSAVE test in sponge samples from normal and EAC patients. These Aims will address important scientific questions while simultaneously advancing the EsoSAVE diagnostic test toward commercial implementation.